Lung Deposition of Droplet Aerosols in Monkeys

Abstract

Nonhuman primates are often the animal models of choice to study the infectivity and therapy of inhaled infectious agents. Most animal models for inhaled infectious diseases use aerosol/droplets generated by an atomization technique such as a Collison nebulizer that produces particles in the size range of 1 to 3 μm in diameter. There are few data in the literature on deposition patterns in monkeys. Our study was designed to measure the deposition pattern in monkeys using droplets having diameters of 2 and 5 μm using an exposure system designed to expose monkeys to aerosols of infectious agents. Six cynomolgus monkeys were exposed to droplets. The aerosol solution was generated from a Vero cell supernate containing DMEM + 10% fetal bovine serum tagged with Tc-99m radiolabel. Collison and Retec nebulizers were used to generate small and large droplets, respectively. The particle size (as determined from a cascade impactor) showed an activity median aerodynamic diameter (AMAD) of 2.3 and 5.1 μm for the Collison and Retec nebulizer, respectively. The animals were anesthetized, placed in a plethysmography box, and exposed to the aerosol. The deposition pattern was determined using a gamma camera. Deposition in the head airways was 39% and 58% for 2.3- and 5.1-μm particle aerosols, respectively, whereas the deposition in the deep lung was 12% and 8%, respectively. This information will be useful in developing animal models for inhaled infectious agents.

This research is supported by The National Biodefense Analysis and Countermeasures Center under contract RSRD-05-00374.